Potassium channels are expressed by all lymphoid cells. A requirement for potassium channels has been demonstrated or inferred during several stages of T lymphocyte development. In peripheral blood lymphocytes they are required for IL2 production. IL2 elaboration and proliferation, therefore can be regulated in vitro by modulating the plasma membrane potassium permeability. There is also a strong correlation between the expression of abnormal potassium channels and the development of clinical disease in several murine genetically inherited immune-mediated lymphoproliferative disorders. Furthermore, during successive maturational stages of normal thymic development three distinct potassium channels of unknown function are expressed by different thymic subpopulations. This pattern of expression is temporally associated with critical maturational events, suggesting that these K+ channels may be involved. Or preliminary experiments evaluating the effect of potassium channel blockers on fetal thymic development support this scenario. They have implicated K+ channels specifically in proliferation of CD4-CD8- fetal thymocytes, TCR expression by CD4+CD8+ fetal thymocytes, and the emergence of mature CD4+CD8- and CD4-CD8+ thymocytes. Our studies will be the first to correlate the expression of multiple K+ channels with specific physiological and immunobiological functions during thymic development. Molecular genetic techniques will be used to systematically identify each potassium channel expressed by every major murine fetal thymocyte subpopulation. The physiologic functions of these involvement of K+ channels i supporting the steady-state membrane potential and in signaling events during intrathymic proliferation and maturation. These studies will elucidate the mechanism by which potassium channels may modulate normal T lymphocyte development in the thymus. It is expect they will also have implications regarding the mechanisms underlying the abnormal development associated with certain lymphoid pathologic conditions and in the future may provide strategies for modulating T cell development in vivo.